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The development of a massively producible vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, is essential for stopping the current coronavirus disease (COVID-19) pandemic. A vaccine must stimulate effective antibody and T cell responses in vivo to induce long-term protection. Scientific researchers have been developing vaccine candidates for the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) since the outbreaks of these diseases. The prevalence of new biotechnologies such as genetic engineering has shed light on the generation of vaccines against novel viruses. In this review, we present the status of the development of coronavirus vaccines, focusing particularly on the biomimetic nanoparticle technology platform, which is likely to have a major role in future developments of personalized medicine., Graphical Abstract Coronavirus vaccine development. COVID-19 is encoded by single-stranded RNA and consists of spike proteins, nucleocapsid proteins, envelope proteins, and membrane proteins. Among them, spike proteins are composed of S1 and S2 subunits, and the receptor binding domain is located on the S1 protein. Coronavirus vaccine development from conventional vaccine to biomimetic nanotechnology vaccine. Image, graphical abstract

Sulforaphane (SFN) is a compound derived from cruciferous plants shown to be effective in cancer prevention and suppression. Myeloid-derived suppressor cells (MDSCs) are known to inhibit anti-tumor immunity; however, whether SFN regulates the anti-tumor activity of MDSCs in breast cancer is still unknown. In the current study, we found that SFN blocked prostaglandin E2 (PGE2) synthesis in parental and doxorubicin (DOX)-resistant breast cancer 4T1 cell lines by activating NF-E2-related factor 2 (Nrf2). Nrf2-mediated reduction of PGE2 was dependent on the enhanced expression of heme oxygenase 1 (HO-1) and glutamate-cysteine ligase (GCLC), and decreased COX-2 expression in breast cancer cells. Moreover, our study further revealed that reduced PGE2 secretion from SFN-treated 4T1 cells triggered MDSCs to switch to an immunogenic phenotype, enhancing the anti-tumor activities of CD8+ T cells. Co-administration of SFN and DOX was more efficacious for the treatment of breast cancer in a mouse model than either agent alone, as evidenced by the significant decrease in tumor volume, MDSC expansion, and increase in cytotoxic CD8+ T cells. Taken together, our data indicate that SFN reverses the immunosuppressive microenvironment and is a potent adjuvant chemotherapeutic candidate in breast cancer.

Purpose Bladder cancer is one of the leading causes of cancer death all over the world, and half of patients are diagnosed at advanced stages with poor therapeutic response. Thus, developing new biomarkers for bladder cancer diagnosis and prognosis is urgently needed. Materials and methods Bioinformatic and gene ontology (GO) analysis were employed to screen highly upregulated and secretory tumor markers in the TCGA BLCA cohort. IHC in tissue microarray and ELISA in cancer cell culture medium were used to validate the expression of putative biomarkers in bladder cancer. Bisulfite sequencing was used to detect DNA methylation status in the promoter of putative genes. Results In this study, MMP11 is first identified as one of the most differentially expressed genes (DEGs) in bladder cancer by meta-analysis in a TCGA bladder cancer cohort. The strong upregulation of MMP11 is confirmed at protein levels in both bladder cancer patients and cell lines. Mechanistic studies reveal that MMP11 promoter hypomethylation, but not genomic amplification or mutation, accounts for its enhanced expression in bladder cancer both in vitro and in vivo. Moreover, clinicopathological analysis indicates that MMP11 upregulation is associated with the tumor progression and poor survival in bladder cancer patients. Discussion These findings suggest that MMP11, as a secretory protein, is a promising biomarker for diagnosis and prognosis in bladder cancer.

Circulating tumor cells (CTCs) play an important role in cancer biology studies. To further elucidate the role of single CTCs in tumor metastasis and prognosis, effective methods must be developed to isolate and encapsulate single CTCs. In this work, a single CTC capture and encapsulation platform based on ZnO nanofibers and surface acoustic waves was constructed. We also demonstrated that this platform can capture and encapsulate single CTCs efficiently. We first validated that the dense ZnO nanofibers provide additional binding sites, resulting in an increased capture efficiency of up to 93.3%. We then demonstrated that the release efficiency was increased to 100% by dissolving the substrate with ultralow concentration (25 mM) phosphoric acid, and the activity of the released cells was not affected. Furthermore, the released cells were suspended in alginate solution and encapsulated single CTCs via droplet-based surface acoustic wave devices. The encapsulating rate of a single cell is up to 13% under a pulse width duration of 520 μs. Few technology based on nanofibers and acoustic tweezers for single-cell encapsulation via acoustic droplet vaporization has been reported. It has a wide range of potential applications to acquire single target cells, which may facilitate further early clinical diagnosis and treatment of cancer patients.

Chronic HCV infection can lead to cirrhosis and is associated with increased mortality. Interleukin (IL)-10-producing B cells (B10 cells) are regulatory cells that suppress cellular immune responses. Here, we aimed to determine whether HCV induces B10 cells and assess the roles of the B10 cells during HCV infection. HCV-induced B10 cells were enriched in CD19hi and CD1dhi CD5+ cell populations. HCV predominantly triggered the TLR2-MyD88-NF-κB and AP-1 signaling pathways to drive IL-10 production by B cells. In a humanized murine model of persistent HCV infection, to neutralize IL-10 produced by B10 cells, mice were treated with pcCD19scFv-IL-10R, which contains the genes coding the anti-CD19 single-chain variable fragment (CD19scFv) and the extracellular domain of IL-10 receptor alpha chain (sIL-10Ra). This treatment resulted in significant reduction of B10 cells in spleen and liver, increase of cytotoxic CD8+ T-cell responses against HCV, and low viral loads in infected humanized mice. Our results indicate that targeting B10 cells via neutralization of IL-10 may offer a novel strategy to enhance anti-HCV immunotherapy.

The protein phosphorylation status of exosomes can regulate the activity and function of proteins related to cancer development, and it is highly possible to diagnose cancers through analyzing the protein phosphorylation status. However, monitoring the protein phosphorylation status with a simple and label-free method is still clinically challenging. Here, inspired by beehives, we developed an Au-coated TiO2 macroporous inverse opal (MIO) structure with an engineered "slow light effect" and thus with outstanding surface-enhanced Raman scattering (SERS) performance. The MIO structure can capture and analyze the exosomes from plasma of cancer patients without any labeling processes. It was found that the SERS intensity of exosomes at 1087 cm-1 arising from the P-O bond within the phosphoproteins can be used as a criterion for tumor liquid biopsies. The intensity of the 1087 cm-1 SERS peak from exosomes extracted from the plasma of cancer patients (prostate, lung, liver, and colon) is at least two times of that from healthy people. This indicates the simplicity and versatility of this method in cancer diagnostics. Our method has obvious advantages (noninvasive and time-saving) over currently clinically used tumor liquid biopsy techniques (such as western blot), which has great potentials to make vitro cancer diagnostics/monitoring as simple as diagnostics/monitoring of common diseases.

Rationale: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world. Apart from traditional surgical resection, radiotherapy, and chemotherapy, more recent techniques such as nano-photothermal therapy and biotherapy are gradually being adopted for the treatment of HCC. This project intends to combine the advantages of nanoscale drug delivery systems with the targeting ability of CAR-T cells. Method: Based on cell membrane-coated nanoparticles and cell membrane-targeting modifications, a novel nanomaterial was prepared by coating CAR-T cell membranes specifically recognizing GPC3+ HCC cells onto mesoporous silica containing IR780 nanoparticles. Subsequently, the physical properties were characterized, and the in vitro and in vivo targeting abilities of this nanoparticle were verified. Results: CAR-T cells were constructed which could recognize GPC3 expressed on the cell surface of HCC cells. Then the isolated CAR-T cell membrane was successfully coated on the IR780 loaded mesoporous silica materials, as verified by transmission electron microscopy. The superior targeting ability of CAR-T cell membrane coated nanoparticles compared to IR780 loaded mesoporous silica nanoparticles was verified, both in vitro and in vivo. Conclusion: This new nanomaterial exhibits photothermal antitumor abilities along with enhanced targeting abilities, suggesting a promising strategy for the treatment of HCC.

Sensing of cytosolic DNA of microbial or cellular/mitochondrial origin by cGAS initiates innate immune responses via the adaptor protein STING. It remains unresolved how the activity of STING is balanced between a productive innate immune response and induction of autoimmunity. Here we show that interferon regulatory factor 8 (IRF8) is essential for efficient activation of STING-mediated innate immune responses in monocytes. This function of IRF8 is independent of its transcriptional role in monocyte differentiation. In uninfected cells, IRF8 remains inactive via sequestration of its IRF-associated domain by its N- and C-terminal tails, which reduces its association with STING. Upon triggering the DNA sensing pathway, IRF8 is phosphorylated at Serine 151 to allow its association with STING via the IRF-associated domain. This is essential for STING polymerization and TBK1-mediated STING and IRF3 phosphorylation. Consistently, IRF8-deficiency impairs host defense against the DNA virus HSV-1, and blocks DNA damage-induced cellular senescence. Bone marrow-derived mononuclear cells which have an autoimmune phenotype due to deficiency of Trex1, respond to IRF-8 deletion with reduced pro-inflammatory cytokine production. Peripheral blood mononuclear cells from systemic lupus erythematosus patients are characterized by elevated phosphorylation of IRF8 at the same Serine residue we find to be important in STING activation, and in these cells STING is hyper-active. Taken together, the transcription-independent function of IRF8 we describe here appears to mediate STING activation and represents an important regulatory step in the cGAS/STING innate immune pathway in monocytes.

Research on circulating tumor cells (CTCs) is of great significance in cancer diagnosis, prognosis and even the development of personalized therapy. Here, we present a simple and transparent acoustofluidic device for CTC separation in a label-free and non-invasive manner, instead of traditional acoustic devices based on silicon substrates, which are not only expensive, but also not conducive to optical visualization. The device is based on cheaper glass fabrication and integrated with a 36°Y-rotated cut lithium niobate single crystal (36° LNO) coated indium tin oxide (ITO) acoustic actuator instead of piezoceramics. It could greatly reduce the generation of heat when the signal is excited by utilizing the thickness vibration mode of the 36° LNO single crystal material because of its super-linear performance. Moreover, pre-aligning the particles in the sample inlet in a two-dimensional (2D) mode served to improve the separation efficiency of the device. It was proved that the separation efficiency of polystyrene particles was 97.1 ± 1.0%. The average separation efficiency of cancer cell lines (MCF7 and HeLa) mixed with white bloods cells was about 91.5 ± 4.5%. Owing to the excellent light transmittance of this acoustofluidic device, it has great potential for application to related optical techniques for cell detection while simultaneously separating cells relying on an acoustic field.

The precise diagnosis of cancer remains a great challenge; therefore, it is our research interest to develop safe, tumor-specific reagents. In this study, we designed nanovesicles derived from erythrocyte membranes; the nanovesicles are capable of recognizing tumor cells for both circulating tumor cell (CTC) capture and tumor imaging. The tumor-targeting molecules folic acid (FA) and fluorescein Cy5 were modified on the nanovesicle surface. The developed nanovesicles exhibit excellent tumor targeting ability both in vitro and in vivo for CTC capture and in tumor imaging. Compared with traditional immunomagnetic beads, the proposed nanovesicles are capable of avoiding non-specific adsorption as a derivative of red blood cells. Combined with a non-invasive means of micromanipulation, the nanometer-sized vesicles show a high purity of CTC capture (over 90%). In vivo, the nanovesicles can also be employed for efficient tumor imaging without obvious toxicity and side effects. In brief, the nanovesicles prepared herein show potential clinical application for integrated diagnosis in vitro and in vivo.

Cryopreservation is a key step for current translational medicine including reproductive medicine, regenerative medicine, and cell therapy. However, it is challenging to preserve rare cells for practical applications due to the difficulty in handling low numbers of cells as well as the lack of highly efficient and biocompatible preservation protocols. Here, we developed an acoustic droplet vitrification method for high-efficiency handling and preservation of rare cells. By employing an acoustic droplet ejection device, we can encapsulate rare cells into water-in-air droplets with a volume from ∼pL to ∼nL and deposit these cell-containing droplets into a droplet array onto a substrate. By incorporating a cooling system into the droplet array substrate, we can vitrify hundreds to thousands of rare cells at an ultrafast speed (about ∼2 s) based on the high surface to volume ratio of the droplets. By optimizing this method with three different cell lines (a human lung cancer cell line, A549 cells, a human liver cell line, L02 cells, and a mouse embryonic fibroblast cell line, 3T3-L1 cells), we developed an effective protocol with excellent cell viability (e.g., >85% for days, >70% for months), proliferation, and adhesion. As a proof-of-concept application, we demonstrated that our method can rapidly handle and efficiently preserve rare cells, highlighting its broad applications in species diversity, basic research, and clinical medicine.

In combating cancer, ultrasound (US)-triggered sonodynamic therapy (SDT) manifests a wide range of promising applications as a noninvasive treatment modality, thus showing potential to overcome the shortcomings and disadvantages of conventional photodynamic therapy (PDT). Reactive oxygen species (ROS)-based therapy is practically destroyed by the high concentration of glutathione (GSH) inside tumors, and depleting GSH to improve the outcome of SDT is indeed a great challenge. Herein, we designed GSH-depleting nanoplatelets for enhanced sonodynamic cancer therapy. A platelet membrane coated nanosystem (PSCI) has been designed and tested comprising mesoporous silica nanoparticles (MSNs) which have been loaded with cinnamaldehyde (CA) as an oxidative stress amplifier. The inner layer comprises the sonosensitizer IR780 and the oxidative stress amplifier CA, whereas the platelet membranes (PM) were designed and utilized as an outer layer that can target tumors, thereby enhancing the effectiveness of SDT by attenuating the capability of tumor cells for scavenging ROS with GSH. SDT and cinnamaldehyde amplify oxidative stress by acting synergistically, leading to the preferential destruction of cancer cells in vitro and in vivo. It is hoped that next-generation tumor SDT treatments will find their way with the help of this strategy.

Background: Cirrhosis is one of the most severe complications at the late stage of chronic HBV infection. The liver biopsy is the gold standard for the diagnosis of liver cirrhosis. However, a liver biopsy is associated with the risk of severe complications and a high cost. It is therefore necessary to find several biomarkers for the diagnosis of HBV-related cirrhosis. Methods: The research was proceeded to evaluate the diagnostic value of hematological parameters to find the surrogate markers in HBV-related cirrhosis. The research was proceeded on the training set, which was recruited from Zhongnan Hospital, including 102 HBV-related cirrhosis and 102 healthy individuals. The levels of selected hematological parameters were analyzed. The receiver operating characteristic curves were generated to evaluate the diagnostic effectiveness of these parameters. A logistic regression model was built and validated using four validation sets consisting of 261 patients.Results: The result show that the level of RDW, MPV, MPV/PC ratio, PLR and NLR were all significantly higher in HBV-related cirrhosis patients compared to healthy individuals. Most of these parameters owned a moderate AUC in HBV-related cirrhosis patients. However, their diagnostic sensitivities or specificities were unsatisfactory. Therefore, a logistic regression model was built by combining these hematological parameters. The model showed great diagnostic value with the AUC of 0.987, sensitivity of 96.1% and specificity of 95.1%. Besides, the other four validation sets were generated to validate the logistic regression model and all showed good AUC with moderate specificities and sensitivities. Conclusions: The data indicate that the model might be substantially useful for the diagnosis of HBV-related cirrhosis.

Asymptomatic transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a potential problem for pandemic control through public health strategies. Our results demonstrate that asymptomatic COVID-19 patients have better outcomes than symptomatic patients. This may have been due to more active cellular immune responses and normal liver function. Since asymptomatic patients have no clinical symptoms which can easily prevent timely diagnosis and treatment, they may cause a greater risk of virus transmission than symptomatic patients, which poses a major challenge to infection control. Evidence suggests that nonpharmaceutical public health interventions, like social distancing and face mask ordinances, play important roles in the control of COVID-19. Looking forward, it may be necessary to proceed cautiously while reopening businesses in areas of epidemicity to prevent potential waves of COVID-19 in the future., Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread around the world. Persons with asymptomatic disease exhibit viral shedding, resulting in transmission, which presents disease control challenges. However, the clinical characteristics of these asymptomatic individuals remain elusive. We collected samples of 25 asymptomatic and 27 symptomatic COVID-19 patients. Viral titers of throat swabs were determined by quantitative reverse transcription-PCR (qRT-PCR). COVID-19 IgG and IgM were examined. Complete blood counts were determined, and serum biochemistry panels were performed. Cytokines, including gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 2 (IL-2), IL-4, IL-6, and IL-10 were evaluated. T cell, B cell, and NK cell counts were measured using flow cytometry. Although similar viral loads were detected, asymptomatic patients had significantly faster virus turnover than symptomatic patients. Additionally, asymptomatic patients had higher counts of lymphocytes, T cells, B cells, and NK cells. While liver damage was observed in symptomatic patients, as indicated by elevated liver enzymes and decreased liver-synthesized proteins in the blood, asymptomatic patients showed normal liver measurements. Lactate dehydrogenase, a COVID-19 risk factor, was significantly lower in asymptomatic patients. These results suggest that asymptomatic COVID-19 patients had normal clinical indicators and faster viral clearance than symptomatic patients. Lymphocytes may play a role in their asymptomatic phenotype. Since asymptomatic patients may be a greater risk of virus transmission than symptomatic patients, public health interventions and a broader range of testing may be necessary for the control of COVID-19. IMPORTANCE Asymptomatic transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a potential problem for pandemic control through public health strategies. Our results demonstrate that asymptomatic COVID-19 patients have better outcomes than symptomatic patients. This may have been due to more active cellular immune responses and normal liver function. Since asymptomatic patients have no clinical symptoms which can easily prevent timely diagnosis and treatment, they may cause a greater risk of virus transmission than symptomatic patients, which poses a major challenge to infection control. Evidence suggests that nonpharmaceutical public health interventions, like social distancing and face mask ordinances, play important roles in the control of COVID-19. Looking forward, it may be necessary to proceed cautiously while reopening businesses in areas of epidemicity to prevent potential waves of COVID-19 in the future.

SARS-CoV-2 is one of the beta-coronaviruses with the spike protein. It invades host cells by binding to angiotensin converting enzyme 2 (ACE2). This newly discovered virus can result in excessive inflammation and immune pathological damage, as shown by a decreased number of peripheral lymphocytes, increased levels of cytokines, and damages of lung, heart, liver, kidney, and other organs. Effective therapeutic modalities such as new antiviral drugs and vaccines against this emerging virus need to be thoroughly studied and developed. However, so far the only recognized but mild progress in this area is the screening of old drugs for new uses. Therefore, rapid and accurate laboratory SARS-CoV-2 testing approaches are the important basis of identification and blockage of COVID-19 transmission. For COVID-19 patients with different clinical classifications (mild, common, severe, and critically severe), dynamic monitoring of functional indicators of susceptible and vital organs is an important strategy for evaluating therapeutic efficacy and prognosis. In this review, we summarized SARS-CoV-2 laboratory diagnostic schemes, pathophysiological indices of tissues and organs of COVID-19 patients, and laboratory diagnostic strategies for distinct disease stages. Further, we discussed the importance of hierarchical management and dynamic observation in SARS-CoV-2 laboratory diagnostics. We then summed up the advance in SARS-CoV-2 testing technology and described the prospect of intelligent medicine in the prevention of infectious disease outbreaks. Graphic abstract Supplementary Information The online version of this article (10.1007/s11010-020-04004-1) contains supplementary material, which is available to authorized users.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued “A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)”; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Hepatocellular carcinoma is the fourth leading cause of cancer-related deaths globally. Advanced nanomaterials have emerged as effective approaches to liver cancer therapy such as photothermal therapy. However, limited penetration depth of photothermal agents (PTAs) activated in the NIR-I bio-window and thermoresistance due to heat shock proteins restrict the therapeutic efficacy of PTT in HCC. Herein, we prepared a Bi@ZIF-8 (BZ) nanomaterial by a simple one-step reduction method. Then, gambogic acid, a natural inhibitor of Hsp90, was efficiently loaded onto the BZ nanomaterial via physical mixing. The characterization of the nanomaterial and release of GA due to pH change or NIR-light irradiation were separately studied. Photothermal conversion efficiency was calculated, and therapeutic studies were carried out in vitro and in vivo. This nanomaterial exhibited a significantly enhanced drug release rate when the temperature was increased under acidic conditions and had good light stability under laser irradiation and a photothermal conversion efficiency of about 24.4%. In addition, this novel nanomaterial achieved good therapeutic effects with less toxicity in vitro. The BZ nanomaterial loaded with GA caused tumor shrinkage as well as disappearance and effectively downregulated Hsp90 expression in tumors in vivo. Moreover, this novel nanomaterial exhibited good biocompatibility and potential for application in low-temperature PTT with excellent tumor destruction efficacy.

Circulating tumor cells (CTCs) are shed into the bloodstream from primary tumors and metastatic lesions and provide significant information about tumor progression and metastasis. CTCs contribute to tumor metastasis through the epithelial-to-mesenchymal transition (EMT). CTC clusters and stem-like phenotypes lead to a more aggressive and metastatic potential. CTCs retain the heterogeneity and imitate the nature of corresponding primary tumors. Therefore, it is important to use single-cell based analysis to obtain information on tumor heterogeneity and biology. CTCs are also good candidates for building preclinical models (especially 3D organoid cultures) for drug screening, disease modeling, genome editing, tumor immunity research, and organ-like biobank establishment. In this article, we summarize the current CTC capture technology, dissect the phenotypes associated with CTC metastasis, and review the progress in single-cell based analysis and preclinical modeling of the pattern and kinetics of CTCs. In particular, we discuss the use of CTCs to assess the progression of hepatocellular carcinoma (HCC).

The COVID-19 pandemic is one of those global challenges that transcends territorial, political, ideological, religious, cultural, and certainly academic boundaries. Public health and healthcare workers are at the frontline, working to contain and to mitigate the spread of this disease. Although intervening biological and immunological responses against viral infection may seem far from the physical sciences and engineering that typically work with inanimate objects, there actually is much that can-and should-be done to help in this global crisis. In this Perspective, we convert the basics of infectious respiratory diseases and viruses into physical sciences and engineering intuitions, and through this exercise, we present examples of questions, hypotheses, and research needs identified based on clinicians' experiences. We hope researchers in the physical sciences and engineering will proactively study these challenges, develop new hypotheses, define new research areas, and work with biological researchers, healthcare, and public health professionals to create user-centered solutions and to inform the general public, so that we can better address the many challenges associated with the transmission and spread of infectious respiratory diseases.

ImportanceA large number of healthcare workers (HCWs) were infected by SARS-CoV-2 during the ongoing outbreak of COVID-19 in Wuhan, China. Hospitals are significant epicenters for the human-to-human transmission of the SARS-CoV-2 for HCWs, patients, and visitors. No data has been reported on the details of hospital environmental contamination status in the epicenter of Wuhan.ObjectiveTo investigate the extent to which SARS-CoV-2 contaminates healthcare settings, including to identify function zones of the hospital with the highest contamination levels and to identify the most contaminated objects, and personal protection equipment (PPE) in Wuhan, China.DesignA field investigation was conducted to collect the surface swabs in various environments in the hospital and a laboratory experiment was conducted to examine the presence of the SARS-CoV-2 RNA.SettingSix hundred twenty-six surface samples were collected within the Zhongnan Medical Center in Wuhan, China in the mist of the COVID-19 outbreak between February 7 - February 27, 2020.ParticipantsDacron swabs were aseptically collected from the surfaces of 13 hospital function zones, five major objects, and three major personal protection equipment (PPE). The SARS-CoV-2 RNAs were detected by reverse transcription-PCR (RT-PCR).Main Outcomes and MeasuresSARS-CoV-2 RNAsResultsThe most contaminated zones were the intensive care unit specialized for taking care of novel coronavirus pneumonia (NCP) (31.9%), Obstetric Isolation Ward specialized for pregnant women with NCP (28.1%), and Isolation Ward for NCP (19.6%). We classified the 13 zones into four contamination levels. The most contaminated objects are self-service printers (20.0%), desktop/keyboard (16.8%), and doorknob (16.0%). Both hand sanitizer dispensers (20.3%) and gloves (15.4%) were most contaminated PPE.Conclusions and RelevanceMany surfaces were contaminated with SARS-CoV-2 across the hospital in various patient care areas, commonly used objects, medical equipment, and PPE. The 13 hospital function zones were classified into four contamination levels. These findings emphasize the urgent need to ensure adequate environmental cleaning, strengthen infection prevention training, and improve infection prevention precautions among HCWs during the outbreak of COVID-19. The findings may have important implications for modifying and developing urgently needed policy to better protect healthcare workers during this ongoing pandemic of SARS-CoV-2.Key PointsQuestionWhat was the hospital setting contamination status, the most contaminated objects and PPE of SARS-CoV-2 during the outbreak of COVID-19 in Wuhan, China?FindingsThe most contaminated zones were the intensive care unit for novel coronavirus pneumonia (NCP) (31.9%), Obstetric Isolation Ward specialized for pregnant women with NCP (28.1%), and Isolation Ward for NCP (19.6%). The most contaminated objects and PPE are self-service printers (20.0%), hand sanitizer dispensers (20.3%), and gloves (15.4%).MeaningThe findings may have important implications for modifying and developing urgently needed policy to better protect healthcare workers during this ongoing pandemic of SARS-CoV-2.

Additional file 2. Search resources and Websites.

Additional file 1. Conflict of Interest Statement form.

Additional file 7. Recommendations list.

Additional file 6. Evidence summary tables.

Additional file 3. Search strategies.

Nano‐radiosensitization is an emerging concept for cancer therapy and the underlying rationale embroils enhancement of radiosensitization by nanomaterials. Here we describe a new concept of the irradiation-triggered switching of a biologically inert nano-prodrug to releasing an anticancer gas that executes cancer cells killing and improves radiosensitization by improving the tumor hypoxic microenvironment. This novel strategy employed chemical coordination between radiosensitive gold-coated polyethylene glycol (PEG) nanoparticles and nanoclusters (AuNCs-PEG) and sodium nitroprusside (SNP) coated by platelet membranes (PM) to generate AuNCs-PEG-SNP-PM (APS), which upon irradiation released a high content of anticancer nitric oxide (NO) through a reaction of SNP and L-glutathione (GSH). NO inhibited cell respiration and O2 consumption through the downregulation of hypoxia inducible factor-1α (HIF-1α). Consequently, O2 accumulation improved therapeutic outcomes by generating ROS in the tumor microenvironment. In preclinical cancer models, we showed that this approach nearly completely eradicated tumors without producing any notable adverse effects. Our therapeutic strategy may provide a new paradigm for effective treatment of various types of cancers.

Background Accumulating evidence has indicated that microRNAs play important roles in the initiation and progression of digestive system tumors. However, previous studies suggest that the accuracy of miRNA detection in digestive system tumors was inconsistent. Methods The candidate miRNAs were obtained from The Cancer Genome Atlas (TCGA). Meta-analysis was performed to evaluate the diagnostic value of these miRNAs in digestive system tumors. Furthermore, the potential target genes of the miRNAs were predicted and assessed with functional analysis. Results According to TCGA data, miR-139 was a common biomarker of digestive system tumors. It was markedly reduced in tumor tissues as compared with non-cancerous tissues in digestive system tumors. In the meta-analysis, the pooled diagnostic odds ratio (DOR) and AUC was 57.51 (95% CI: 14.25–232.04) and 0.96 (95% CI: 0.94–0.97), respectively. Furthermore, the overall sensitivity and specificity was 0.89 (95% CI: 0.73–0.96) and 0.91 (95% CI: 0.75–0.97), respectively. The diagnostic value of tissue miR-139 was higher than the diagnostic value of blood miR-139. In particular, miR-139 was a superior marker for distinguishing colorectal cancer. Conclusion miR-139 could be a potential biomarker for diagnosis of digestive system tumors especially colorectal cancer.

Background Tissue biopsy-based cancer diagnosis has limitations because of the fact that tumor tissues are in constant evolution and extremely heterogeneous. The current study was aimed to examine whether tumor-educated blood platelets (TEPs) might be a potential all-in-one source for blood-based cancer diagnostics to overcome the limitations of conventional cancer biopsy. Methods In the present study, we evaluated the expression pattern of MAGI2 antisense RNA 3 (MAGI2-AS3) and ZNFX1 antisense RNA 1 (ZFAS1) in both plasma and platelets of 101 non-small-cell lung cancer (NSCLC) patients. Receiver operating characteristic (ROC) curve was generated to evaluate their diagnostic potential. In addition, epidermal growth factor receptor (EGFR) mutations were detected in DNA and RNA samples of platelets for companion diagnostics. Results Our results showed that the levels of MAGI2-AS3 and ZFAS1 in both plasma and platelets of NSCLC patients were significantly downregulated than those in healthy controls. A positive correlation of long noncoding RNA expression was observed between platelets and plasma (r=0.738 for MAGI2-AS3, r=0.751 for ZFAS1, respectively). By ROC analysis, we found that molecular interrogation of MAGI2-AS3 and ZFAS1 in TEPs and plasma can offer valuable diagnostic performance for NSCLC patients (area under the ROC curve [AUC] MAGI2-AS3 = 0.853/0.892, and AUC ZFAS1 =0.780/0.744 for diagnosing adenocarcinoma and squamous cell carcinoma cases from controls, respectively). Clinicopathologic characteristic analysis further revealed that MAGI2-AS3 level significantly correlated with tumor-node-metastasis (TNM) stage (p=0.001 in TEPs, p=0.003 in plasma), lymph-node metastasis (p=0.016 in TEPs, p=0.023 in plasma), and distant metastasis (p=0.045 in TEPs, p=0.045 in plasma), while ZFAS1 level was only correlated with TNM stage (p=0.005 in TEPs, p=0.044 in plasma). Furthermore, EGFRvIII RNA existed in both TEPs and plasma, but EGFR intracellular mutations cannot be detected in DNA of TEPs isolated from NSCLC. Conclusion Our data suggested that TEP is a promising source for NSCLC diagnosis and companion diagnostics.

To capture both epithelial and mesenchymal subpopulations of CTCs at different metastatic stages of PCa patients, here we constructed a novel dual-antibody-functionalized microfluidic device by employing antibodies against PSMA and EpCAM. In vitro experiments with the dual capture system for capturing both LnCAP and LnCAP-EMT cells have shown significantly enhanced capture efficiency as compared to that of the EpCAM single capture system. Furthermore, the dual capture system could successfully identify CTCs in 20 out of 24 (83.3%) PCa patients, and the CTCs counts from the dual capture system were statistically correlated with the TNM stage of patients ( P0.05), while conventional diagnostic methods, such as serum PSA level and Gleason score, failed to correlate to patient TNM stages. To further explore potential clinical application of our dual capture system, captured CTCs were recovered and subjected to qRT-PCR to quantify known factors involved in PCa development and therapy. The results demonstrated that the combined detection of SChLAP1 and PSA in CTCs is a potential marker for identifying patients with metastatic PCa, while detection of AR and PD-L1 in CTCs may have the potential to determine the sensitivity of PCa patients to androgen deprivation therapy and immunotherapy, respectively. Taken together, the dual-antibody-functionalized microfluidic device established in our study overcomes the limitations of some CTC capture platforms that only detect epithelial or mesenchymal CTCs in PCa patients, and detection of the PCa-related RNA signatures from purified CTCs holds great promise to offer warnings for early metastasis of PCa and may provide guidance for therapy decisions.

Background: Circulating tumor cells (CTCs) are a burgeoning topic in cancer biomarker discovery research with minimal invasive blood draws. CTCs can be used as potential biomarkers for disease prognosis, early cancer diagnosis and pharmacodynamics. However, the extremely low abundance of CTCs limits their clinical utility because of technical challenges such as the isolation and subsequent detailed molecular and functional characterization of rare CTCs from patient blood samples. Methods: In this study, we present a novel density gradient centrifugation method employing biodegradable gelatin nanoparticles coated on silicon beads for the isolation, release, and downstream analysis of CTCs from colorectal and breast cancer patients. Results: Using clinical patient/spiked samples, we demonstrate that this method has significant CTC-capture efficiency (>80%) and purity (>85%), high CTC release efficiency (94%) and viability (92.5%). We also demonstrate the unparalleled robustness of our method in downstream CTC analyses such as the detection of PIK3CA mutations. Conclusion: The efficiency and versatility of the multifunctional density microbeads approach provides new opportunities for personalized cancer diagnostics and treatments.

Nanocancer medicine, such as photothermal therapy (PTT), as a promising way to solve cancer without side effects, faces a huge biological barrier during the circulation of nanoparticles in the body, including nanobiological interactions in the blood, isolation of nanoparticles in the macrophage system, tumor spillover effect, and especially uneven intratumoral distribution of nanoparticles, which cast a shadow over the hope. To address the problem of intratumoral distribution, an effective photothermal agent is introduced by packaging the black phosphorus quantum dots (BPQDs) into exosome vector (EXO) through electroporation method. With the improving and proper stability for better therapy, the resulting BPQDs@EXO nanospheres (BEs) exhibit good biocompatibility, long circulation time, and excellent tumor targeting ability, hence impressive PTT efficiency evidenced by highly efficient tumor ablation in vivo. Importantly, great permeability on organoids contributed by EXO appears with BEs, which strongly promotes the efficient killing ability. These BP-based nanospheres must promise high clinical potential due to the high PTT efficiency and minimal side effects.

BACKGROUND It is now widely acknowledged that chronic inflammation is closely associated with the process of cancer development. As a simple noninvasive blood-based test, hematological parameters in the routine blood test have been considered as inflammation markers. We aimed to evaluate platelet count (PC), red blood cell distribution width (RDW), white blood cell count (WBC), mean platelet volume (MPV), number of neutrophils/lymphocytes ratio (NLR), and platelet count/lymphocytes ratio (PLR) as surrogate inflammatory markers in breast cancer (BC) patients, and we compared these to those in healthy individuals. MATERIAL AND METHODS A retrospective study was conducted in Zhongnan Hospital of Wuhan University from July 2014 to April 2015, including 110 cases of pathologically diagnosed BC patients and 78 cases of healthy females. Retrospective analysis of selected hematological parameters was performed between the 2 groups, as well as assessment of the correlation between these indexes and clinicopathological characteristics of the 110 breast cancer patients. RESULTS The mean values of RDW, MPV, NLR, and PLR were significantly higher in BC patients compared to the control group. The level of MPV exhibited positive correlations with lymph node metastasis and the Ki67 proliferation index in preoperative BC patients (P

We have designed a biochip-based mRNA detection device by combining a hydrophilic–hydrophobic micropattern with upconversion luminescence (UCL) probes., Development of a portable device for the detection of multiple mRNAs is a significant need in the early diagnosis of cancer. We have designed a biochip-based mRNA detection device by combining a hydrophilic–hydrophobic micropattern with upconversion luminescence (UCL) probes. The device achieves highly sensitive detection, using the naked eye, of multiple mRNAs among patient samples. The high sensitivity is attributed to enrichment of the target concentration and a fluorescence enhancement effect. In addition, since the photonic crystal (PC) dot biochip is functionalized with dual-wavelength excitation UCL probes, two kinds of mRNAs in the heterogeneous biological samples are detected simultaneously, and the corresponding luminescence signals are captured using an unmodified camera phone. The biochip-based mRNA detection device reported here demonstrates that multiple mRNAs extracted from patient samples can be simultaneously and sensitively detected in a visual way without sophisticated instrumentation. Therefore, this device is promising for real-time detection of multiple biomarkers in patient samples, and it is anticipated that it will provide a powerful tool for convenient early diagnosis of cancer.

α-Fetoprotein is commonly used in the diagnosis of hepatocellular carcinoma. However, the diagnostic significance of α-fetoprotein has been questioned because a number of patients with hepatocellular carcinoma are α-fetoprotein negative. It is therefore necessary to develop novel noninvasive techniques for the early diagnosis of hepatocellular carcinoma, particularly when α-fetoprotein level is low or negative. The current study aimed to evaluate the diagnostic efficiency of hematological parameters to determine which can act as surrogate markers in α-fetoprotein–negative hepatocellular carcinoma. Therefore, a retrospective study was conducted on a training set recruited from Zhongnan Hospital of Wuhan University—including 171 α-fetoprotein–negative patients with hepatocellular carcinoma and 102 healthy individuals. The results show that mean values of mean platelet volume, red blood cell distribution width, mean platelet volume–PC ratio, neutrophils–lymphocytes ratio, and platelet count–lymphocytes ratio were significantly higher in patients with hepatocellular carcinoma in comparison to the healthy individuals. Most of these parameters showed moderate area under the curve in α-fetoprotein–negative patients with hepatocellular carcinoma, but their sensitivities or specificities were not satisfactory enough. So, we built a logistic regression model combining multiple hematological parameters. This model presented better diagnostic efficiency with area under the curve of 0.922, sensitivity of 83.0%, and specificity of 93.1%. In addition, the 4 validation sets from different hospitals were used to validate the model. They all showed good area under the curve with satisfactory sensitivities or specificities. These data indicate that the logistic regression model combining multiple hematological parameters has better diagnostic efficiency, and they might be helpful for the early diagnosis for α-fetoprotein–negative hepatocellular carcinoma.

Colorectal cancer (CRC) is one of the most frequent cancers occurring in developed countries. Distant CRC metastasis causes more than 90% of CRC-associated mortality. MicroRNAs (miRNAs) play a key role in regulating tumor metastasis and could be potential diagnostic biomarkers in CRC patients. This study is aimed at identifying miRNAs that can be used as diagnostic biomarkers for CRC metastasis. Towards this goal, we compared the expression of five miRNAs commonly associated with metastasis (i.e., miR-10b, miR-200c, miR-155, miR-21, and miR-31) between primary CRC (pCRC) tissues and corresponding metastatic lymph nodes (mCRC). Further, bioinformatics analysis of miR-31 was performed to predict target genes and related signaling pathways. Results showed that miR-31, miR-21, miR-10b, and miR-155 expression was increased to different extents, while miR-200c expression was lower in mCRC than that in pCRC. Moreover, we found that the level of both miR-31 and miR-21 was notably increased in pCRC when lymph node metastasis (LNM) was present, and the increase of miR-31 expression was more profound. Hence, upregulated miR-31 and miR-21 expression might be a miRNA signature in CRC metastasis. Moreover, we detected a higher miR-31 level in the plasma of CRC patients with LNM compared to patients without LNM or healthy individuals. With the bioinformatics analysis of miR-31, 121 putative target genes and transition of mitotic cell cycle and Wnt signaling pathway were identified to possibly play a role in CRC progression. We next identified seven hub genes via module analysis; of these, TNS1 was most likely to be the target of miR-31 and had significant prognostic value for CRC patients. In conclusion, miR-31 is significantly increased in the cancer tissues and plasma of CRC patients with LNM; thus, a high level of miR-31 in the plasma is a potential biomarker for the diagnosis of LNM of CRC.

Supplemental Material, Table_S1_and_S2 for A Logistic Regression Model for Noninvasive Prediction of AFP-Negative Hepatocellular Carcinoma by Chang-Liang Luo, Yuan Rong, Hao Chen, Wu-Wen Zhang, Long Wu, Diao Wei, Xiu-Qi Wei, Lie-Jun Mei and Fu-Bing Wang in Technology in Cancer Research & Treatment

Objective: To investigate the potential biomarkers for venous metastasis of hepatocellular carcinoma (HCC), and briefly discuss their target genes and the signaling pathways they are involved in. Materials and Method: The dataset GSE6857 was downloaded from GEO. Significantly differentially expressed miRNAs were identified using the R package “limma,” After that, the survival analysis was conducted to discover the significance of these up-regulated miRNAs for the prognosis of HCC patients. Additionally, miRNAs which were up-regulated in venous metastasis positive HCC tissues and were significant for the prognosis of HCC patients were further verified in clinical samples using RT-qPCR. The miRNAs were then analyzed for their correlations with clinical characteristics including survival time, AFP level, pathological grade, TNM stage, tumor stage, lymph-node metastasis, distant metastasis, child-pugh score, vascular invasion, liver fibrosis and race using 375 HCC samples downloaded from the TCGA database. The target genes of these miRNAs were obtained using a miRNA target gene prediction database, and their functions were analyzed using the online tool DAVID. Results: 15 miRNAs were differentially expressed in samples with venous metastasis, among which 7 were up-regulated in venous metastasis positive HCC samples. As one of the up-regulated miRNAs, hsa-miR-210 was identified as an independent prognostic factor for HCC. Using RT-qPCR, it was evident that hsa-miR-210 expression was significantly higher in venous metastasis positive HCC samples (p = 0.0036). Further analysis indicated that hsa-miR-210 was positively associated with AFP level, pathological grade, TNM stage, tumor stage and vascular invasion. A total of 168 hsa-miR-210 target genes, which are mainly related to tumor metastasis and tumor signaling pathways, were also predicted in this study. Conclusion: hsa-miR-210 might promote vascular invasion of HCC cells and could be used as a prognostic biomarker.